II. Indications
- T-Cell Lymphoma (relapsed or refractory)
III. Contraindications
- Caution in Chronic Kidney Disease
IV. Mechanism
- Anti-Folate agent active as an antineoplastic and Immunosuppressant
- Targets cells expressing RFC-1 (reduced Folate carrier-1)
-
Folate analog inhibitor of dihydrofolate reductase (DHFR)
- Blocks Tetrahydrofolate synthesis
- Depletes Nucleotide precursors
- Inhibits DNA, RNA and Protein synthesis
V. Medications
- Pralatrexate IV Solution 20 mg/ml in 1 to 2 ml vials
VI. Dosing
- See other references for disease specific dosing protocols
- Adult: 30 mg/m2 IV once weekly for 6 weeks, followed by 1 week of no Pralatrexate
- Coadministered agents to reduce adverse effects (e.g. mucositis)
- Folic Acid 1 to 1.25 mcg orally daily
- Start 10 days before, and continue for 30 days after last Pralatrexate dose
- Vitamin B12 1000 mcg IM
- Give one dose within 10 weeks of starting Pralatrexate
- Repeat Vitamin B12 dosing every 10 weeks while taking Pralatrexate
- Folic Acid 1 to 1.25 mcg orally daily
VII. Adverse Effects
- Hepatotoxicity
- Myelosuppression
- Mucositis
- Life-Threatening Drug-Induced Rashes (e.g. Toxic Epidermal Necrolysis)
VIII. Safety
- Avoid in Pregnancy (any trimester)
- Use reliable Contraception
- Avoid in Lactation
IX. Drug Interactions
- Drugs that prolong Pralatrexate activity (decreased clearance)
X. Resources
- Pralatrexate (DailyMed)
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Related Studies
Definition (NCI) | A folate analogue inhibitor of dihydrofolate reductase (DHFR) exhibiting high affinity for reduced folate carrier-1 (RFC-1) with antineoplastic and immunosuppressive activities. Pralatrexate selectively enters cells expressing RFC-1; intracellularly, this agent is highly polyglutamylated and competes for the folate binding site of DHFR, blocking tetrahydrofolate synthesis, which may result in depletion of nucleotide precursors; inhibition of DNA, RNA and protein synthesis; and apoptotic tumor cell death. Efficient intracellular polyglutamylation of pralatrexate results in higher intracellular concentrations compared to non-polyglutamylated pralatrexate, which is more readily effuxed by the MRP (multidrug resistance protein) drug efflux pump. RFC-1, an oncofetal protein expressed at highest levels during embryonic development, may be over-expressed on the cell surfaces of various cancer cell types. |
Definition (NCI_NCI-GLOSS) | A drug used in the treatment of peripheral T-cell lymphoma (a fast-growing form of non-Hodgkin lymphoma). It is also being studied in the treatment of other types of cancer. Pralatrexate may block the growth of cancer cells and cause them to die. It is a type of dihydrofolate reductase (DHFR) inhibitor. |
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C418863 |
SnomedCT | 429320009, 428598004 |
English | Pralatrexate (product), Pralatrexate (substance), pralatrexate, Pralatrexate, PRALATREXATE, PRALAtrexate |
Spanish | pralatrexato (sustancia), pralatrexato (producto), pralatrexato |